1. DiGiulio, Sarah

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Is it time for more precision medicine in pediatric oncology? The field's thought leaders said "yes" in a review article published last year in the journal Science (2019:363;1175-1181).

Katherine A. Janeway... - Click to enlarge in new windowKatherine A. Janeway, MD. Katherine A. Janeway, MD

Precision medicine-more specifically, treating cancers with drugs targeted to those tumors' genetic alterations-is making possible a plethora of advances in the treatment of adult cancers. And there's evidence the approach could help move the needle when it comes to the treatment of cancers in childhood, too, the Science review's authors note.


"Pediatric cancers harbor certain genomic alterations that are rarely seen in adult cancers, and for many of these alterations, molecularly targeted therapies do not yet exist. [Also], pediatric cancers share some genomic alterations and mutational gene signatures with adult cancers, and for a subset of these alterations, molecularly targeted therapies already exist," the coauthors wrote in the review.


"Importantly, for only a small proportion (5-10%) of these pediatric cancers, there is clinical trial evidence showing that the genomic alteration predicts the response to the targeted drug. Thus, there is an urgent need for precision clinical trials in pediatric cancers," according to the review.


More basket trials and umbrella trials will help match molecularly targeted drugs with the cancers they are most likely to help with in children. Accelerating early-phase trials could help, as could incorporating more combination therapies into precision medicine trials. And recent regulatory changes will help, too, the review notes.


We caught up with paper coauthor Katherine A. Janeway, MD, a pediatric hematologist-oncologist at Dana-Farber/Boston Children's Cancer and Blood Disorders Center (who is also Director of Clinical Genomics at Dana-Farber Cancer Institute), about the topics discussed in this paper and progress that's being made.


1 What would you say are still some of the biggest barriers in the way of more precision medicine in pediatric oncology?

"There are several barriers. The greatest barrier has been access to precision therapies for children with cancer. In addition, a number of the central genomic events that could serve as molecular targets in childhood cancer are more difficult to inhibit with drugs. The best example of this is fusion oncogenes that result in abnormally active transcription factors. An example is the diagnosis-defining transcription factor fusion EWSR1-FLI1 in Ewing sarcoma, which was identified over 20 years ago, and yet trials of drugs targeting this molecular target have only recently begun.


"We've made some significant progress in understanding the pediatric cancer genome and in translating that knowledge to the clinic. But, there is much more progress to be made. Fortunately, recent updates to policy should facilitate rapid advancements in pediatric precision cancer medicine."


2 Can you elaborate on what those regulatory changes are and other steps you think are most promising in changing this paradigm and bringing more precision medicine to pediatric oncology?

"The implementation of the RACE for Children Act (the Research to Accelerate Cures and Equity for Children Act) and FDA guidance regarding adolescent patient clinical trials eligibility will further increase the number and types of clinical trials of molecularly targeted trials in biomarker-defined patient populations for children with cancer.


"Clinical trials written primarily for adults now fairly often allow patients 12 and older to participate.


"This paradigm is already changing as a result of: 1) an increasing amount of sequencing data from pediatric cancers plus greater accessibility to this data; 2) a greater number of biomarker-defined standard phase I, II, and basket trials; and 3) a focus on developing molecularly targeted therapies for the 'undruggable' targets prevalent in pediatric cancers with a particular focus on fusion oncoproteins."


3 What is the bottom-line takeaway message that oncologists and cancer care providers should know about opportunities for precision medicine in pediatric oncology?

"The next 5 years will be a very exciting time in pediatric precision oncology. We will see more sequencing performed routinely in the clinic; there will be a greater number of clinical trials of molecularly targeted therapies for young cancer patients; and basic science investigators will make inroads into developing drugs tackling the more challenging drug targets common in pediatric cancers."